کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2542742 | 1122734 | 2006 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The pharmacokinetics and acute renal effects of oral microemulsion ciclosporin A in normal pigs The pharmacokinetics and acute renal effects of oral microemulsion ciclosporin A in normal pigs](/preview/png/2542742.png)
BackgroundThe use of ciclosporin A (CsA) is limited by nephrotoxicity. Anatomic and physiologic similarities to humans make the pig a potential important animal model for research in effects and adverse events of CsA. In a long-term study CsA 10 mg/kg/day for 6 months did not cause deterioration in renal histology or function in pigs. For ideal CsA dosage in future long-term studies of nephrotoxicity we performed this study to describe pharmacokinetics and acute effects on renal function of CsA in normal pigs.Materials and methodsThree groups of 5 piglets comprised the material, a control group and 2 groups receiving 5 days treatment with CsA (Neoral) 15 or 30 mg/kg/day, respectively. CsA whole blood concentration (B-CsA) (hourly), renal blood flow, glomerular filtration rate (GFR) and serum creatinine were measured. The area under the curve from time 0 to 12 h was calculated using the Trapezoidal Rule. Pharmacokinetic calculations were performed using the KINFIT non-linear curve fitting module.ResultsB-CsA reached peak in median at 0.90 and 0.96 h (633 and 914 ng/ml) in the 15 and 30 mg/kg/day groups, respectively, and median AUC was 5055 and 6275 h ng/ml, respectively. Trough levels were 338 and 475 ng/ml. The distribution of CsA followed a 2-compartment model. Serum creatinine was 111 (control), 112 (15 mg/kg/day) and significantly increased to 168 ìmol/l in 30 mg/kg/day group, which also had a reduction in GFR compared to the other 2 groups.ConclusionsCsA causes acute nephrotoxicity in piglets. The distribution follows a 2-compartment model similar to humans, but higher doses are necessary in pigs.
Journal: International Immunopharmacology - Volume 6, Issue 4, April 2006, Pages 627–634